Sodium-glucose co-transporter inhibitor dapagliflozin attenuates cognitive deficits in sporadic Alzheimer’s rat model

Ayşe Nur Hazar-yavuz; Muhammet Emin Çam; Levent Kabasakal

Makale detayları

Sodium-glucose co-transporter inhibitor dapagliflozin attenuates cognitive deficits in sporadic Alzheimer’s rat model

Yazarlar:

Ayşe Nur Hazar-yavuz | Muhammet Emin Çam | Levent Kabasakal

Yayıncı:

Marmara University

Ana Başlıklar:

Medical Pharmacology

Dergi:

Journal of Research in Pharmacy Vol.26 Issue 2, pp.298-310

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001346338

pISSN:

2630-6344

Anahtar kelimeler:

Özet:

 Alzheimers disease AD and Type 2 Diabetes Mellitus T2DM are both characterized by similar pathologies, and studies have shown that various drugs from both groups may be effective in another. The effects of sodium-glucose co-transporter SGLT2 inhibitors in AD are unknown. According to molecular docking studies, various SGLT inhibitors have acetylcholinesterase AChE inhibition activity, which is therapeutic target for AD. In this study, we investigated the effects of SGLT2 inhibitor dapagliflozin on intracerebroventricular icv streptozotocin STZ induced sporadic AD rats using open field test OFT, novel object recognition test NORT, passive avoidance test PAT and Morriss water maze test MWMT. Rats were randomly divided into 4 groups: vehicle-control, icv STZ, dapagliflozin, and galantamine treatments groups. STZ was injected bilaterally in two divided doses on day 1 and 3. All treatments began on day 1 and continued to day 21. OFT was performed for evaluating animal locomotor activity and anxiety. Other behavioral tests, NORT, PAT, and MWMT was performed for determining of learning and memory ability of rats. On day 21, all rats were decapitated. Our results showed that treatments with dapagliflozin and galantamine significantly prevented learning and memory deficits in behavioral tests. Dapagliflozin may present as a potent dual inhibitor of SGLT2 and AChE. Our results may form the basis of future dual treatment against diabetes and diabetes-related neurological diseases. The effects of possible dual AChE and SGLT2 inhibition by a single compound may help to establish new drugs that perform both anti-AD and antidiabetic action.

 Alzheimers disease AD and Type 2 Diabetes Mellitus T2DM are both characterized by similar pathologies, and studies have shown that various drugs from both groups may be effective in another. The effects of sodium-glucose co-transporter SGLT2 inhibitors in AD are unknown. According to molecular docking studies, various SGLT inhibitors have acetylcholinesterase AChE inhibition activity, which is therapeutic target for AD. In this study, we investigated the effects of SGLT2 inhibitor dapagliflozin on intracerebroventricular icv streptozotocin STZ induced sporadic AD rats using open field test OFT, novel object recognition test NORT, passive avoidance test PAT and Morriss water maze test MWMT. Rats were randomly divided into 4 groups: vehicle-control, icv STZ, dapagliflozin, and galantamine treatments groups. STZ was injected bilaterally in two divided doses on day 1 and 3. All treatments began on day 1 and continued to day 21. OFT was performed for evaluating animal locomotor activity and anxiety. Other behavioral tests, NORT, PAT, and MWMT was performed for determining of learning and memory ability of rats. On day 21, all rats were decapitated. Our results showed that treatments with dapagliflozin and galantamine significantly prevented learning and memory deficits in behavioral tests. Dapagliflozin may present as a potent dual inhibitor of SGLT2 and AChE. Our results may form the basis of future dual treatment against diabetes and diabetes-related neurological diseases. The effects of possible dual AChE and SGLT2 inhibition by a single compound may help to establish new drugs that perform both anti-AD and antidiabetic action.

 Alzheimers disease AD and Type 2 Diabetes Mellitus T2DM are both characterized by similar pathologies, and studies have shown that various drugs from both groups may be effective in another. The effects of sodium-glucose co-transporter SGLT2 inhibitors in AD are unknown. According to molecular docking studies, various SGLT inhibitors have acetylcholinesterase AChE inhibition activity, which is therapeutic target for AD. In this study, we investigated the effects of SGLT2 inhibitor dapagliflozin on intracerebroventricular icv streptozotocin STZ induced sporadic AD rats using open field test OFT, novel object recognition test NORT, passive avoidance test PAT and Morriss water maze test MWMT. Rats were randomly divided into 4 groups: vehicle-control, icv STZ, dapagliflozin, and galantamine treatments groups. STZ was injected bilaterally in two divided doses on day 1 and 3. All treatments began on day 1 and continued to day 21. OFT was performed for evaluating animal locomotor activity and anxiety. Other behavioral tests, NORT, PAT, and MWMT was performed for determining of learning and memory ability of rats. On day 21, all rats were decapitated. Our results showed that treatments with dapagliflozin and galantamine significantly prevented learning and memory deficits in behavioral tests. Dapagliflozin may present as a potent dual inhibitor of SGLT2 and AChE. Our results may form the basis of future dual treatment against diabetes and diabetes-related neurological diseases. The effects of possible dual AChE and SGLT2 inhibition by a single compound may help to establish new drugs that perform both anti-AD and antidiabetic action.

 Alzheimers disease AD and Type 2 Diabetes Mellitus T2DM are both characterized by similar pathologies, and studies have shown that various drugs from both groups may be effective in another. The effects of sodium-glucose co-transporter SGLT2 inhibitors in AD are unknown. According to molecular docking studies, various SGLT inhibitors have acetylcholinesterase AChE inhibition activity, which is therapeutic target for AD. In this study, we investigated the effects of SGLT2 inhibitor dapagliflozin on intracerebroventricular icv streptozotocin STZ induced sporadic AD rats using open field test OFT, novel object recognition test NORT, passive avoidance test PAT and Morriss water maze test MWMT. Rats were randomly divided into 4 groups: vehicle-control, icv STZ, dapagliflozin, and galantamine treatments groups. STZ was injected bilaterally in two divided doses on day 1 and 3. All treatments began on day 1 and continued to day 21. OFT was performed for evaluating animal locomotor activity and anxiety. Other behavioral tests, NORT, PAT, and MWMT was performed for determining of learning and memory ability of rats. On day 21, all rats were decapitated. Our results showed that treatments with dapagliflozin and galantamine significantly prevented learning and memory deficits in behavioral tests. Dapagliflozin may present as a potent dual inhibitor of SGLT2 and AChE. Our results may form the basis of future dual treatment against diabetes and diabetes-related neurological diseases. The effects of possible dual AChE and SGLT2 inhibition by a single compound may help to establish new drugs that perform both anti-AD and antidiabetic action.

Makale detayları

Sodium-glucose co-transporter inhibitor dapagliflozin attenuates cognitive deficits in sporadic Alzheimer’s rat model

Yazarlar:

Ayşe Nur Hazar-yavuz | Muhammet Emin Çam | Levent Kabasakal

Yayıncı:

Marmara University

Ana Başlıklar:

Medical Pharmacology

Dergi:

Journal of Research in Pharmacy Vol.26 Issue 2, pp.298-310

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001346338

pISSN:

2630-6344

Dapagliflozin

Alzheimer’s disease

type 2 diabetes mellitus

sodium-glucose co-transporter inhibitor

Sayı

Makale detayları

Sodium-glucose co-transporter inhibitor dapagliflozin attenuates cognitive deficits in sporadic Alzheimer’s rat model

Yazarlar: Ayşe Nur Hazar-yavuz | Muhammet Emin Çam | Levent Kabasakal

Yayıncı: Marmara University

Ana Başlıklar: Medical Pharmacology

Dergi: Journal of Research in Pharmacy Vol.26 Issue 2, pp.298-310

Belge Tipi: Makale

Yayın Tarihi: 6/2025

Belge Dili: İngilizce

Document ID (Org No.): 2001346338

pISSN: 2630-6344

Dapagliflozin

Alzheimer’s disease

type 2 diabetes mellitus

sodium-glucose co-transporter inhibitor

Sayı

Yazarlar:

Ayşe Nur Hazar-yavuz | Muhammet Emin Çam | Levent Kabasakal

Yayıncı:

Marmara University

Ana Başlıklar:

Medical Pharmacology

Dergi:

Journal of Research in Pharmacy Vol.26 Issue 2, pp.298-310

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001346338

pISSN:

2630-6344